Developing RNA Vaccines to Treat Peanut Hypersensitivity

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Project Summary/Abstract: Oral immunotherapy with PALFORZIA® is a recently FDA-approved therapy to treat peanut allergy. This therapy requires daily doses of characterized peanut proteins administered orally to peanut hypersensitive individuals. A major limitation of the PALFORZIA® therapy is the potential for the onset of allergic responses and possibly anaphylaxis due to activation of peanut-specific IgE coated mast cells. Development of hypoallergenic peanut proteins devoid of IgE-mediated granulocyte activation potential may address the known safety limitations of therapy with PALFORZIA®. The rise of the SARS-CoV-2 pandemic and rapid production and dissemination of mRNA COVID vaccines has highlighted the benefits of mRNA vaccines to protect against infectious diseases. The goal of this project is to utilize mRNA vaccine technology to express peanut proteins that lack and/or disrupt known IgE epitopes to provide a peanut allergen vaccine that does not induce allergic reactions in hosts hypersensitive to the native allergen. This proposal will utilize the dominant peanut allergen, Ara h 2, which is recognized by majority of peanut allergic individuals and is sufficient to induce hypersensitivity in mice, to develop mRNA vaccines that produce native Ara h 2 or mutant Ara h 2 with mutations in known linear IgE epitopes. The studies described in this proposal will evaluate in vitro protein production, in vitro IgE-mediated granulocyte activation, in vivo immunogenicity, and in vivo allergic disease activation in hosts sensitized to the native allergen. The results from this proposal will generate proof-of-concept preliminary data to support future studies to develop mRNA vaccines expressing multiple peanut proteins to treat peanut- hypersensitivity in allergic hosts.